In the last few years the incidence of drug abuse and addiction in our society has been on a dramatic increase. We propose here a complete study of the pharmacokinetics of two of these highly abused drugs-- cocaine and d-Amphetamine. The choice of the Rhesus monkey as the test animal was made because of the similarity to his fellow primate, man, in his willingness to self-administer drugs that man abuses. For the first time a study will undertake to directly correlate the pharmacodynamics of a drug with changes in self-administration behavior in the test animal. In addition, the quantitative data obtained will enable a complete analysis of the type of tolerance which develops after use of d- amphetamine. Furthermore, the fact that cocaine has not been demonstrated to cause development of tolerance in man or the Rhesus monkey will be investigated. The behavioral parameters to be studied timing behavior as well as continuous avoidance. The metabolic pathway of elimination of both drugs (cocaine and d- amphetamine) will be extensively explored by the use of a GC-Mass Spec system. This data will help explain the change in primate metabolism which can be caused by chronic dosage of either drug. Throughout the self-administration studies which will be performed with both drugs on varying conditions, the blood level of the drug in the subject will be monitored so a clear relationship between changes in behavioral pattern and drug level in the body can be made. Major metabolites whether known or discovered in either study will be tested for reinforcing efficacy. An attempt will also be made to determine the pharmacodynamic properties which can be altered and cause a change in self- administration pattern.